Correlations between surface composition and aerosolization of jet-milled dry powder inhaler formulations with pharmaceutical lubricants.

Co-jet-milling drugs and lubricants may enable simultaneous particle size reduction and surface coating to achieve satisfactory aerosolization performance. This study aims to establish the relationship between surface lubricant coverage and aerosolization behavior of a model drug (ciprofloxacin HCl) co-jet-milled with lubricants [magnesium stearate (MgSt) or l-leucine]. The co-jet-milled formulations were characterized for particle size, morphology, cohesion, Carr's index, and aerosolization performance. The surface lubricant coating was assessed by probing surface chemical composition using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary-ion mass spectrometry (ToF-SIMS). The effects of co-jet-milling on the surface energy and in vitro dissolution of ciprofloxacin were also evaluated. Our results indicated that, in general, the ciprofloxacin co-jet-milled with l-leucine at >0.5% w/w showed a significant higher fine particle fraction (FPF) compared with the ciprofloxacin jet-milled alone. The FPF values plateau at or above 5% w/w for both MgSt and l-leucine. We have established the quantitative correlations between surface lubricant coverage and aerosolization in the tested range for each of the lubricants. More importantly, our results suggest different mechanisms to improve aerosolization for MgSt-coating and l-leucine-coating, respectively: MgSt-coating reduces inter-particulate interactions through the formation of low surface energy coating films, while l-leucine-coating not only reduces the surface energy but also creates rough particle surfaces that reduce inter-particulate contact area. Furthermore, surface coatings with 5% w/w MgSt (which is hydrophobic) did not lead to substantial changes in in vitro dissolution. Our findings have shown that the coating structure/quality and their effects could be highly dependent on the process and the coating material. The findings from this mechanistic study provide fundamental understanding of the critical effects of MgSt and l-leucine surface coverages on aerosolization and powder flow properties of inhalation particles.

Near-Ambient-Pressure X-ray Photoelectron Spectroscopy Study of Methane-Induced Carbon Deposition on Clean and Copper-Modified Polycrystalline Nickel Materials.

In order to simulate solid-oxide fuel cell (SOFC)-related coking mechanisms of Ni, methane-induced surface carbide and carbon growth was studied under close-to-real conditions by synchrotron-based near-ambient-pressure (NAP) X-ray photoelectron spectroscopy (XPS) in the temperature region between 250 and 600 °C. Two complementary polycrystalline Ni samples were used, namely, Ni foam-serving as a model structure for bulk Ni in cermet materials such as Ni/YSZ-and Ni foil. The growth mechanism of graphene/graphite species was found to be closely related to that previously described for ethylene-induced graphene growth on Ni(111). After a sufficiently long "incubation" period of the Ni foam in methane at 0.2 mbar and temperatures around 400 °C, cooling down to ∼250 °C, and keeping the sample at this temperature for 50-60 min, initial formation of a near-surface carbide phase was observed, which exhibited the same spectroscopic fingerprint as the C2H4 induced Ni2C phase on Ni(111). Only in the presence of this carbidic species, subsequent graphene/graphite nucleation and growth was observed. Vice versa, the absence of this species excluded further graphene/graphite formation. At temperatures above 400 °C, decomposition/bulk dissolution of the graphene/graphite phase was observed on the rather "open" surface of the Ni foam. In contrast, Ni foil showed-under otherwise identical conditions-predominant formation of unreactive amorphous carbon, which can only be removed at ≥500 °C by oxidative clean-off. Moreover, the complete suppression of carbide and subsequent graphene/graphite formation by Cu-alloying of the Ni foam and by addition of water to the methane atmosphere was verified.